4-amino-5-fluoro-2-methoxybenzonitrile

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-amino-5-fluoro-2-methoxybenzonitrile (intermediate 88; 5.3 g, 0.03 mol) in ethanol (20 mL) was added sodium hydroxide 8M (27.9 mL, 0.22 mol), the mixture was placed in a sealed vessel and heated to 110° C. for 20 hours. The solvent was removed under reduced pressure and the crude obtained was partitioned between water and ether. The aqueous layer was acidified by hydrochloric acid 6N until pH 4 and the crude was extracted with ethyl acetate, dried, filtered and evaporated under reduced pressure giving the title compound as a yellow solid (80%), which was used in the next step without further purification. the mixture was placed in a sealed vessel The solvent was removed under reduced pressure the crude obtained was partitioned between water and ether the crude was extracted with ethyl acetate dried filtered evaporated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-amino-5-fluoro-2-methoxybenzonitrile (intermediate 88; 5.3 g, 0.03 mol) in ethanol (20 mL) was added sodium hydroxide 8M (27.9 mL, 0.22 mol), the mixture was placed in a sealed vessel and heated to 110° C. for 20 hours. The solvent was removed under reduced pressure and the crude obtained was partitioned between water and ether. The aqueous layer was acidified by hydrochloric acid 6N until pH 4 and the crude was extracted with ethyl acetate, dried, filtered and evaporated under reduced pressure giving the title compound as a yellow solid (80%), which was used in the next step without further purification. the mixture was placed in a sealed vessel The solvent was removed under reduced pressure the crude obtained was partitioned between water and ether the crude was extracted with ethyl acetate dried filtered evaporated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of methanol (10.48 mL, 0.25 mol) and anh. tetrahydrofuran (60 mL) was added dropwise a solution of potassium tert-butilate (6.76 g, 0.05 mol) in anh. tetrahydrofuran (52 mL) at 0° C. under nitrogen atmosphere. The mixture was stirred for minutes at room temperature and then 4-amino-2,5-difluorobenzonitrile (4 g, 0.02 mol) was added. The reaction mixture was stirred at 70° C. for 3 hours. The solvent was partially removed and ether was added into the mixture. The organic layer was washed with bicarbonate and brine, dried and filtered. The organic solvent was removed under reduced pressure to give the title compound as a yellow solid (97%), which was used in the next step without further purification. The reaction mixture was stirred at 70° C. for 3 hours The solvent was partially removed ether was added into the mixture The organic layer was washed with bicarbonate and brine dried filtered The organic solvent was removed under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-amino-5-fluoro-2-methoxybenzonitrile (intermediate 88; 5.3 g, 0.03 mol) in ethanol (20 mL) was added sodium hydroxide 8M (27.9 mL, 0.22 mol), the mixture was placed in a sealed vessel and heated to 110° C. for 20 hours. The solvent was removed under reduced pressure and the crude obtained was partitioned between water and ether. The aqueous layer was acidified by hydrochloric acid 6N until pH 4 and the crude was extracted with ethyl acetate, dried, filtered and evaporated under reduced pressure giving the title compound as a yellow solid (80%), which was used in the next step without further purification. the mixture was placed in a sealed vessel The solvent was removed under reduced pressure the crude obtained was partitioned between water and ether the crude was extracted with ethyl acetate dried filtered evaporated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of methanol (10.48 mL, 0.25 mol) and anh. tetrahydrofuran (60 mL) was added dropwise a solution of potassium tert-butilate (6.76 g, 0.05 mol) in anh. tetrahydrofuran (52 mL) at 0° C. under nitrogen atmosphere. The mixture was stirred for minutes at room temperature and then 4-amino-2,5-difluorobenzonitrile (4 g, 0.02 mol) was added. The reaction mixture was stirred at 70° C. for 3 hours. The solvent was partially removed and ether was added into the mixture. The organic layer was washed with bicarbonate and brine, dried and filtered. The organic solvent was removed under reduced pressure to give the title compound as a yellow solid (97%), which was used in the next step without further purification. The reaction mixture was stirred at 70° C. for 3 hours The solvent was partially removed ether was added into the mixture The organic layer was washed with bicarbonate and brine dried filtered The organic solvent was removed under reduced pressure